THERAPEUTIC EFFECT OF KRM-1648 WITH VARIOUS ANTIMICROBIALS AGAINST MYCOBACTERIUM-AVIUM COMPLEX INFECTION IN MICE

A new benzoxazinorifamycin, KRM-1648 (KRM), was studied for its therap eutic efficacy in combination with other antimicrobials against Mycoba cterium avium complex infections in mice. When M. intracellulare-infec ted (intravenously) mice were given KRM, clarithromycin (CAM), sparflo xacin (SPFX), or ethambutol (EB) each alone or in combination, by gava ge, once daily 6 times per week (streptomycin [SM] was given subcutane ously twice per week) from day 1, KRM + CAM exhibited combined efficac y in terms of reducing the incidence of gross lung lesions and the bac terial loads in the lungs and spleens. The addition of either EB or EB + SPFX to KRM + CAM increased the efficacy. Moreover, the multi-drug regimen of KRM + CAM + EB + SPFX (or ofloxacin [OFLX]) was more effica cious than rifampicin (RMP) + CAM + EB + SPFX (or OFLX). In M. avium i nfection, KRM + clofazimine was the most efficacious among two-drug co mbinations tested followed by KRM + SM. KRM + CAM was considerably les s effective against M. avium than against M. intracellulare infection. KRM + EB and KRM + OFLX failed to show such a combined effect.